Analgesic effect of antidepressant drugs.
Imipramine, amitriptyline, citalopram, and maprotiline were examined in different models of a nociceptive reaction after single-dose, and 21-day long administration, in rats. Animals' behavior in the Porsolt and open-field tests was also studied to compare analgesic and antidepressant-like action of drugs and to check the contribution of changes in the rats' gross behavior to animals' reactions to the nociceptive stimuli. The time- and dose-dependent fluctuations in the blood and brain concentrations of imipramine were evaluated in another group of animals. Imipramine, amitriptyline, citalopram, and maprotiline were shown to exert analgesic activity in some tests only. The most unequivocal analgesic effects were observed in the writhing test (2% acetic acid solution I.P.). The antinociceptive action of antidepressants in this test was probably not due to their local anaesthetic activity, because it was also present after intragastric drugs administration. Alterations in the open-field behavior of rats subjected to the treatment with antidepressant drugs did not correlate with animals' behavior in the writhing test. In the Porsolt test, the antidespair effects of antidepressants were not observed after acute drugs administration at the doses effective in the writhing test. Moreover, in contrary to the writhing reaction, the antiimmobility effect was potently enhanced after repeated administration of tricyclic drugs. Additionally, no association was found between the blood and brain concentrations of chronically administered imipramine and its effects in the writhing test. The obtained results indicate: (a) disparate sensitivity to antidepressant treatment of differently evoked behavioral reactions to the nociceptive stimuli; (b) the most potent effects of administered antidepressants in the model of visceral pain; (c) a better correlation of the brain concentration of imipramine with its antiimmobility than analgesic effect: (d) the lack of relationship between the analgesic and antidepressant-like effects of examined antidepressants compounds.
Korzeniewska-Rybicka
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Department of Experimental and Clinical Pharmacology, Medical Academy, Warsaw, Poland.
Płaźnik
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D000700:Analgesics / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry; D004305:Dose-Response Relationship, Drug; D016231:Fluorescence Polarization Immunoassay; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
D000700:Analgesics; D000928:Antidepressive Agents